Preosteoblasts and fibroblasts respond differently to anatase titanium dioxide nanoparticles: A cytotoxicity and inflammation study

There is a bundle of proofs suggesting that some industrial nanoparticles (NPs) can provoke diseases and pollute the environment durably. However, these issues still remain controversial. In the biomedical field, TiO2 NPs were recently proposed to serve as fillers in polymeric materials to improve bone prostheses and scaffolds. Submicrometer TiO2 particles could also result from wear debris of prostheses. Thus, it appears to be of the highest importance to elucidate the effects of well-characterized TiO2 NPs on the behaviour of osteoblasts. In this work, we have measured the toxicity of anatase TiO2 NPs with two different cell types, on L929 fibroblasts and for the first time on MC-3T3 pre-osteoblasts, with the aim to determine the level of cellular toxicity and inflammation. Our results clearly show that these NPs provoke different dose–response effects, with the pre-osteoblasts being much more sensitive than fibroblasts. Furthermore, we observed that anatase TiO2 NPs had no effect on cell adhesion. By contrast, both cell types had their morphology and LDH release modified in the presence of NPs. Their DNA was also found to be fragmented as analyzed by quantifying the sub-G1 cell population with flow cytometry. By measuring the production of IL-6 and TNF-α proinflammatory cytokines, we have shown that TNF-α was never produced and that MC-3T3 cells were secreting IL-6. Most importantly, our results highlight the necessity of evaluating the toxicity of prostheses wear debris, and of NP coatings of medical implants, to determine if they can possibly provoke inflammation and inhibit bone reconstruction.